Cancer
Cancer accounts for nearly one-quarter of deaths in the United States, exceeded only by heart disease. In the year 2000, there were 553,091 cancer deaths in the US. In 2003, the American Cancer Society estimates that this number will increase to approximately 556,500, due to aging and growth of the population. Lung cancer is the most common fatal cancer in men (31%), followed by prostate (10%), and colon & rectum (10%). In women, lung (25%), breast (15%), and colon & rectum (11%) are the leading sites of cancer death. Among children, leukemia is the most common cancer among children ages 0-14 years and it comprises approximately 30% of all childhood cancers and accounts for the most childhood deaths. Acute lymphocytic cancer is the most common form of leukemia in children. It is estimated that 1.33 million new cases of cancer were diagnosed in 2003 (American Cancer Society, 2003 Cancer Statistics Slide Set 2003).
Melanoma
Studies have indicated that nearly 45,000 new cases of melanoma are diagnosed each year in the U.S., and approximately 20% of patients will die of metastatic disease. Melanomas arise from the malignant conversion of melanocytes, which in turn are derived from mesenchymal neural crest cells. Melanomas undergo melanogenesis, a complex process that results in the production of melanin. Melanogenesis is initiated by the hydroxylation of L-tyrosine, to form L-dihydroxyphenylalanine (L-DOPA), which is then converted to DOPAchrome by specific melanocyte-associated enzymes, including tyrosinase. A further series of oxidation and reduction reactions ultimately convert DOPAchrome to melanin. It has been suggested that melanogenesis may account for the resistance of melanomas to treatment with ionizing radiation and chemotherapy. It has also been suggested that byproducts of melanogenesis are responsible for other adverse effects including immunosuppression, fibrosis and mutagenesis.
Current Treatments
Chemotherapy (CT) and radiation therapy (RT), and combinations thereof, remain the leading defenses against cancer, although recent advances in the field have led to widespread uses of specialized treatments such as angiogenesis inhibitors, biological therapies, including adjuvant therapy to boost the patient's immune system, antibody therapy, vaccine therapy, and photodynamic therapy.
In addition to numerous adverse effects of RT and CT, a major limiting factor is the development of drug resistance by the tumors, and induction of tumor cell growth arrest and senescence. While senescent tumors do not increase in size per se, they still retain the capacity to produce and secrete tumor stimulating mitogens and pro-angiogenic factors that can lead to tumor progression.
The present invention shows that the sodium salt of the 4-(allylamino)benzoic acid derivative C-45 has unexpected benefits for the treatment of melanotic tumors and non-melanotic tumors. Further, the sodium salt of C-45 can surprisingly can potentiate treatment of melanotic and non-melanotic carcinomas with RT and/or CT.